Abstract
Transcription factors are master switches for various biochemical pathways. However, transcription factors involved in the pathogenesis of ovarian cancer have yet to be explored thoroughly. Therefore, in the present study, we assessed the prognostic value of the transcription factor E74-like factor 3 (ELF3) identified via transcriptome profiling of the epithelial components of microdissected ovarian tumor samples isolated from long- and short-term survivors and determined its roles in ovarian cancer pathogenesis. Immunohistochemical analysis of ELF3 in tumor tissue sections suggested that ELF3 was exclusively expressed by epithelial ovarian cancer cells. Furthermore, using 112 high-grade ovarian cancer samples isolated from patients and The Cancer Genome Atlas (TCGA) data, we found that downregulation of ELF3 expression was markedly associated with reduced survival. Functional studies demonstrated that overexpression of ELF3 in ovarian cancer cells suppressed proliferation and anchorage-dependent growth of the cells and that ELF3 silencing increased cell proliferation. Furthermore, upregulation of ELF3 increased expression of epithelial markers, decreased expression of mesenchymal markers, and mediated translocation of epithelial-mesenchymal transition (EMT) signaling molecules in ovarian cancer cells. Finally, we validated the tumor-inhibitory roles of ELF3 using animal models. In conclusion, ELF3 is a favorable prognostic marker for ovarian cancer. As a negative regulator of EMT, ELF3-modulated reversal of EMT may be a new effective modality in the treatment of ovarian cancer.
Highlights
Ovarian cancer is the fifth most common form of cancer in women in the United States
Because E74-like factor 3 (ELF3) has been associated with epithelial cell differentiation [9, 10], we selected it for further validation and functional studies
The results showed significantly lower ELF3 expression levels in high-grade serous ovarian carcinoma (HGSC) samples than in serous borderline ovarian tumor (SBOT) and low-grade serous ovarian cancer (LGSC) samples (p < 0.001 and p < 0.017, respectively) (Figure 1C)
Summary
Ovarian cancer is the fifth most common form of cancer in women in the United States. For 2016, researchers estimated the occurrence of 22,280 new cases of and 14,240 deaths due to ovarian cancer in the United States [1]. Ovarian cancer is notable for its initial sensitivity (> 75% response rates) to combination chemotherapy with platinum agents and taxane following debulking surgery. The vast majority of women receiving this combination treatment (> 75–80%) will have cancer recurrence within 12–24 months after the initial diagnosis and die of progressively chemotherapy-resistant disease. Prognostic factors for ovarian cancer include 1) stage, 2) grade of the tumor, 3) degree of debulking surgery, and 4) degree of platinum/taxane sensitivity. Investigators have yet to validate the prognostic and functional significance of a majority of differentially expressed genes in ovarian tumors
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